Work in this laboratory (Singer et al., Int. J. Biochem., 4 (1973) 569-574) established originally that aged humans had about one third the number of cytoplasmic glucocorticoid receptor binding sites and other binding proteins as cytosols from livers of young adults. Since then, other laboratories have confirmed this with animal experiments. Our recent investigations on a wide range of tissue culture cell lines suggest that the glucocorticoid receptor is invariably expressed, even in totipotent teratocarcinoma cells (relatively highly undifferentiated cells) leading inescapably to the conclusion that glucocorticoid receptor may be essential for survival of mammalian cells. Consequently we will study the regulation of the glucocorticoid receptor as a function of age. If the cause of lowered receptor binding sites in old animals can be determined, something fundamental may be learned about the aging process itself. Regulation will include: the relative amounts of translocation inhibitor; the characterization of "young" and "old" receptor from liver and kidney; endocrine manipulations and subsequent determination of numbers of receptor binding sites in cytosol and nuclei, and the characterization of different forms of nuclear bound steroid-receptor complex. Glucocorticoid activated cytosol DNA-binding proteins, other than the glucocorticoid receptor, will be separated and characterized in young and old rats.